Abstract
The purpose of this study was to evaluate the pharmacokinetics of tulathromycin in the plasma and maternal and fetal tissues of pregnant ewes when administered within 24 hours of a single, IV Campylobacter jejuni (C. jejuni) challenge. Twelve, pregnant ewes between 72–92 days of gestation were challenged IV with C. jejuni IA3902 and then treated with 1.1 ml/45.36 kg of tulathromycin subcutaneously 18 hours post-challenge. Ewes were bled at predetermined time points and euthanized either at a predetermined time point or following the observation of vaginal bleeding or abortion. Following euthanasia, tissues were collected for bacterial culture, pharmacokinetics and histologic examination. The maximum (geometric) mean tulathromycin plasma concentration was estimated at 0.302 μg/mL, with a peak level observed at around 1.2 hours. The apparent systemic clearance of tulathromycin was estimated at 16.6 L/h (or 0.28 L/kg/h) with an elimination half-life estimated at approximately 22 hours. The mean tissue concentrations were highest in the uterus (2.464 μg/g) and placentome (0.484 μg/g), and were lowest in fetal liver (0.11 μg/g) and fetal lung (0.03 μg/g). Compared to previous reports, results of this study demonstrate that prior IV administration of C. jejuni appeared to substantially alter the pharmacokinetics of tulathromycin, reducing both the peak plasma concentrations and elimination half-life. However, additional controlled trials are required to confirm those observations.
Highlights
Infection with Campylobacter spp. is one of the most common causes of ovine abortion throughout the world and has been reported to be the most common infectious cause of ovine abortion in the United States [1,2,3]
The vast majority of recent US C. jejuni isolates are reported to be resistant to tetracyclines, and pharmacokinetic studies have shown that feeding chlortetracycline to sheep at the approved dose (80 mg/head/day), or at an even higher, unapproved dose (500 mg/head/day), resulted in levels that were presumed to be subtherapeutic in pregnant ewe plasma and largely undetectable in fetal tissues and amniotic fluid [1,6,7,8,9]
Susceptibility results on C. jejuni isolates from field cases of ovine abortion demonstrate that the vast majority are currently susceptible to macrolide antibiotics, including tulathromycin, azithromycin, telithromycin and erythromycin [1,8,9] The potential benefits of treating sheep with a macrolide antibiotic such as tulathromycin include the ease of administration, its wide volume of distribution, low effective plasma concentrations, and long terminal half-life, which has been reported to be 110.8 h (± 20.9) in pregnant ewes [10,11]
Summary
Infection with Campylobacter spp. is one of the most common causes of ovine abortion throughout the world and has been reported to be the most common infectious cause of ovine abortion in the United States [1,2,3]. The vast majority of recent US C. jejuni isolates are reported to be resistant to tetracyclines (including chlortetracycline), and pharmacokinetic studies have shown that feeding chlortetracycline to sheep at the approved dose (80 mg/head/day), or at an even higher, unapproved dose (500 mg/head/day), resulted in levels that were presumed to be subtherapeutic in pregnant ewe plasma and largely undetectable in fetal tissues and amniotic fluid [1,6,7,8,9]. The potential clinical effectiveness of tulathromycin in C. jejuni exposed pregnant ewes has been confirmed in a study utilizing an IV C. jejuni challenge model in which tulathromycin treatment resulted in a statistically significant (p < .05) decrease in the rate of vaginal bleeding/abortion in pregnant ewes compared to untreated controls [12]
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